Synthesis and activity studies on novel 6-methoxybenzothiazole-piperazine derivatives with propanamide chain

In this study, ten novel compounds, bearing N-(6-methoxybenzothiazol-2-yl)-3-(4-substituedpiperazinyl)propanamide backbone were synthesized. In vitro antibacterial and antifungal activity were determined using of Ofloxacin and Nystatin as standards respectively. To obtain starting compound, 2-amino-6-methoxybenzothiazole was acylated with 3-chloropropionyl chloride. After substitution of chlorine in 3-chloro-N-(6-methoxy-1,3-benzothiazol-2-yl)propanamide by different piperazine derivatives, the target compounds were obtained. Structure elucidation of the synthesized compounds were confirmed by UV, FT-IR, 1H-NMR, 13C-NMR, mass spectral and elemental analysis methods. In addition, their antibacterial and antifungal activity were evaluated in vitro by agar-based disc diffusion and minimum inhibitory concentration assays against Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 15442), Escherichia coli (ATCC 11229) and Candida albicans (ATCC 10231) strains. According to activity results, the most active compounds were compounds 2 and 5 against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans with (inhibition zone: 12 mm). Docking studies were performed to predict the interactions of compounds in test set with DNA gyrase subunit B of S. aureus. Under light of docking studies, a new compound with promising GyrB inhibition was designed. Keywords: Antimicrobial, benzothiazole, piperazine, antibacterial, antifungal.